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Molecular and Cellular Biology, March 2004, p. 2584-2592, Vol. 24, No. 6
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.6.2584-2592.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Absence of an Essential Role for Thymic Stromal Lymphopoietin Receptor in Murine B-Cell Development

Nick Carpino,1 William E. Thierfelder,1,{dagger} Ming-shi Chang,2,{ddagger} Chris Saris,2 Steven J. Turner,3 Steven F. Ziegler,4,{dagger} and James N. Ihle1,5*

Department of Biochemistry,1 Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,4 Department of Functional Genomics, Amgen Inc., Thousand Oaks, California 91320,2 Department of Microbiology and Immunology, University of Melbourne, Melbourne, Victoria 3010, Australia,3 Benaroya Research Institute at Virginia Mason, Seattle, Washington 981015

Received 24 October 2003/ Returned for modification 8 December 2003/ Accepted 20 December 2003

The murine cytokine thymic stromal lymphopoietin (TSLP) supports the development of B220+ IgM+ immature B cells and induces thymocyte proliferation in vitro. Human TSLP, by contrast, activates CD11c+ dendritic cells, but not B or T cells. Recent studies have demonstrated that the receptor for TSLP consists of a heterodimer of the interleukin 7 (IL-7) {alpha} chain and a novel protein that resembles the hematopoietic cytokine receptor common {gamma} chain. We examined signal transduction by the {gamma}-like chains using chimeric receptor proteins. The cytoplasmic domain of the human, but not of the murine, {gamma}-like chain, activates Jak2 and Stat5 and supports the proliferation of hematopoietic cell lines. In order to assess the role of the murine {gamma}-like chain in vivo, we generated {gamma}-like chain-deficient mice. Receptor-deficient mice are unresponsive to TSLP but exhibit no obvious phenotypic defects. In particular, hematopoietic cell development appeared normal. B-cell development, including the IgM+ compartment, was unaffected by loss of the TSLP pathway, as were T lymphopoiesis and lymphocyte proliferation in vitro. Cytokine receptors that utilize the common {gamma} chain signal through the lymphocyte-specific kinase Jak3. Mice deficient in Jak3 exhibit a SCID phenotype but harbor a residual B220+ splenic lymphocyte population. We demonstrate here that this residual lymphocyte population is lost in mice lacking both the {gamma}-like chain and Jak3.

* Corresponding author. Mailing address: Howard Hughes Medical Institute, St. Jude Children's Research Hospital, Memphis, TN 38105. Phone: (901) 495-3422. Fax: (901) 525-8025. E-mail: james.ihle{at}stjude.org.

{dagger} Present address: Department of Natural Sciences and Mathematics, Crichton College, Memphis, TN 38111.

{ddagger} Present address: Department of Biochemistry, Medical College, National Cheng-kung University, Tainan, Taiwan.

Molecular and Cellular Biology, March 2004, p. 2584-2592, Vol. 24, No. 6
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.6.2584-2592.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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